Related Experiment Video
Updated: Oct 18, 2025
09:58
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
13.9K
Rutaecarpine Increases Anticancer Drug Sensitivity in Drug-Resistant Cells through MARCH8-Dependent ABCB1
Tingting Zou1, Cheng Zeng1, Junyan Qu1
1School of Life Sciences, Chongqing University, Chongqing 401331, China.
Biomedicines
|September 28, 2021
Summary
Rutaecarpine reverses multidrug resistance (MDR) by reducing ABCB1 protein levels. This natural compound upregulates MARCH8, promoting ABCB1 degradation and enhancing chemotherapy effectiveness against cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) in cancer, often mediated by ABCB1 (P-glycoprotein), leads to chemotherapy failure.
- Inhibiting ABCB1 is crucial for restoring chemotherapeutic drug efficacy.
- Identifying novel strategies to overcome MDR is a significant clinical challenge.
Purpose of the Study:
- To investigate the potential of rutaecarpine, a natural alkaloid, in reversing ABCB1-mediated MDR.
- To elucidate the molecular mechanism by which rutaecarpine exerts its MDR-reversing effects.
- To evaluate the therapeutic potential of combining rutaecarpine with conventional anticancer agents.
Main Methods:
- Assessed rutaecarpine's ability to reverse ABCB1-mediated MDR in cancer cells.
- Investigated the effect of rutaecarpine on ABCB1 protein and mRNA levels.
- Identified and characterized the interaction between ABCB1 and the E3 ubiquitin ligase MARCH8.
- Examined the impact of rutaecarpine on MARCH8 expression and its role in ABCB1 degradation.
- Evaluated the efficacy of combination therapy in a transplanted tumor model.
Main Results:
- Rutaecarpine demonstrated significant reversal of ABCB1-mediated MDR.
- The reversal effect was attributed to the attenuation of ABCB1 protein levels.
- ABCB1 was identified as a substrate of MARCH8, which promotes its ubiquitination and degradation.
- Rutaecarpine upregulated MARCH8 protein levels, enhancing ABCB1 degradation.
- Combination treatment with rutaecarpine and anticancer drugs showed therapeutic effects on transplanted tumors.
Conclusions:
- Rutaecarpine effectively overcomes ABCB1-mediated multidrug resistance by promoting ABCB1 degradation via upregulation of MARCH8.
- This study reveals a novel mechanism involving MARCH8 in regulating ABCB1 stability.
- Co-administration of rutaecarpine with chemotherapeutic agents presents a promising strategy to enhance cancer treatment efficacy and overcome MDR.
More Related Videos
Related Concept Videos
02:56Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
02:34Inhibition of Cdk Activity
5.0K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
02:57Targeted Cancer Therapies
8.0K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.0K
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
02:50Combination Therapies and Personalized Medicine
5.2K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.2K
02:23Abnormal Proliferation
4.7K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K